This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Metabolic Syndrome is a highly prevalent condition that is comprised of several major clustering factors that increase the risk for developing cardiovascular disease (CVD). [41-43] The hallmarks of Metabolic Syndrome are discussed later in the protocol, however, insulin resistance, glucose intolerance, and/or Diabetes Mellitus (DM) are contributing factors to a diagnosis of Metabolic Syndrome. However, if the patient has DM alone, then he/she is still at risk for developing CVD, as insulin resistance on its own is associated with vascular changes. [38, 39] These disturbances can be seen down to the level of the microvasculature. Further, these vascular disturbances also lead to nerve damage and neuropathy. Diabetic Peripheral Neuropathy (DPN) is a condition brought on by prolonged exposure to high blood glucose. Interestingly, neuropathy can also modulate vascular reactivity and hence alter circulation. [44] Thus, it is important to monitor microvascular changes in patients to assess their disease progression and cardiovascular risks. Microvascular disturbances include abnormalities in arteriolar reactivity, capillary recruitment, permeability, and blood flow. [45] These changes are evident in both Metabolic Syndrome and DM patients. There are varying degrees of these disruptions, and the defects in small vessel structure and function can be observed very early in life and early in disease. [45] Therefore screening for microvascular changes in patients predisposed to the development of DM, Metabolic Syndrome, or CVD should provide a means to evaluate both progression towards a given disease state as well as the advancement of that disease. Thus, studying microvascular changes in patients may be of clinical importance in diseased patients as well as at-risk patients;however, there are no established, non-invasive, accurate, and easy ways to measure these changes at clinics. A tool that would allow clinicians to non-invasively measure changes in the microvasculature (for example, by quantifying the change in concentrations of deoxyhemoglobin and oxyhemoglobin in the microvasculature in response to metabolic stress) in an outpatient clinic, could allow for earlier detection and long-term monitoring of patients. This would allow more time for preventative care and treatment. This research project, in collaboration with partners at the Beckman Laser Institute, aims to evaluate the hypothesis that a novel technology known as Diffuse Optical Spectroscopy (DOS) can be used to non-invasively measure changes in the microvasculature of patients. DOS is a technique that measures the optical absorption and scattering properties of near-infrared light in tissues such as muscle in order to quantify the absolute concentration of oxygenated and deoxygenated hemoglobin, water, and lipids. It provides quantitative and functional information on the microvasculature related to tissue perfusion, metabolic changes, and indicators of tissue damage. It has shown promise in the field of breast cancer, and we seek to evaluate the potential of DOS as a means to measure microvascular changes in Metabolic Syndrome and DM patients in order to assess CVD risk.